Association of hypoxia-inducible factor-1 expression with histology in epithelial ovarian tumors: a quantitative analysis of HIF-1.
BACKGROUND
Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor that mediates cellular and systemic homeostatic responses to reduced oxygen availability in mammals. So far, using immunohistochemistry we have analyzed the association of HIF-1alpha expression with histological type among epithelial ovarian tumors. In the present study, quantitative analyses of activated HIF-1 level in the nucleus and of accumulated HIF-1alpha level in the cytoplasm were performed to clarify whether or not the hypoxic state would be correlated to histology, malignancy, and tumor size in epithelial ovarian tumors.


METHODS
HIF-1 level in the nucleus was analyzed using DNA binding assay, and HIF-1alpha level in the cytoplasm was measured by ELISA for a total of 36 epithelial ovarian tumors as follows: 5 serous adenocarcinomas (SEAs), 7 clear cell adenocarcinomas (CLAs), 7 endometrioid adenocarcinomas (ENAs), 4 mucinous adenocarcinomas (MUAs), 2 mucinous borderline tumors (MBTs), and 11 mucinous adenomas.


RESULTS
HIF-1 level (mg/ml) in the nucleus and HIF-1alpha level (mg/ml) in the cytoplasm were on average 0.116 and 0.178 for SEAs, 0.328 and 0.306 for CLAs, 0.171 and 0.305 for ENAs, 0.097 and 0.176 for MUAs, 0.224 and 0.180 for mucinous borderline tumors, 0.152 and 0.154 for mucinous adenomas. CLAs showed the highest levels for both of HIF-1 and HIF-1alpha, while MUAs showed the lowest levels of both. Mucinous adenomas were higher in HIF-1 than MUAs.


CONCLUSIONS
Hypoxic state was considered to be closely related to histological type of epithelial ovarian tumors, suggesting that CLAs may be most hypoxic. In the comparison of mucinous tumors, malignancies would not always become most hypoxic. Tumor size may not be strongly associated with hypoxic state.
Miyazawa
Masaki
M
Department of Pathology, Tokai University, Tokyo, Japan.
Yasuda
Masanori
M
Fujita
Mariko
M
Hirasawa
Takeshi
T
Kajiwara
Hiroshi
H
Hirabayashi
Kenichi
K
Ogane
Naoki
N
Shimizu
Michio
M
Asanuma
Hideki
H
Murakami
Masaru
M
Takekoshi
Susumu
S
Mikami
Mikio
M
Osamura
R Yoshiyuki
RY
D000230:Adenocarcinoma / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D055815:Young Adult
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D004247:DNA